by Chan Hei. / "July 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 235-247). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

HOX proteins are evolutionarily conserved homeodomain-containing transcription factors involved in hematopoiesis and patterning during embryogenesis. Their tasks as master regulators of embryonic development are achieved in large part through their ability to interact with co-factors of the PBX and MEIS/PREP families, which constitute the broader three amino-acid loop extension (TALE) class of homeodomain proteins. HOX, MEIS, and PBX have been implicated in leukemic hematopoiesis due to their association with hematological malignancies. The oncogenic function of MEIS1 in accelerating the onset of acute myeloid leukemia induced by HOX was mapped to its C-terminal transactivation domain, which is responsive to PKA signaling. This thesis extends our understanding regarding the mechanism by which MEIS1A executes its C-terminal transactivation function in vivo. We describe the involvement of CREB and its co-activators CBP and TORC in conferring the PKA-responsiveness of the ME1S1A C terminus. CREB mutants that fail to bind CBP or TORC also fail to promote PKA induction mediated by the C terminus of ME1S1A. TORC was further shown to be capable of bypassing the need for PKA to activate transcription by MEIS1, an ability endowed by its physical interaction with MEIS1. Chromatin immunoprecipitation (ChIP) demonstrated a concerted recruitment of endogenous MEIS1, TORC2, and CREB proteins on ME1S1 target genes. In addition, this thesis also characterizes the promoter of the murine Meis1 gene. Meis1 possesses multiple transcription start sites upstream of its translation initiation site. We identified a ME1S·PBX consensus recognition site within the Meis1 promoter and showed that PBX1 binds to this sequence in vitro. Our ChIP assay results further suggest an autoregulatory mode for the Meis1 gene as revealed by a co-occupancy of endogenous CREB, TORC2, PBX1, and MEIS1 itself on the Meis1 promoter. Collectively, this thesis proposes a mechanistic action conferred by CREB, CBP and TORC in the PKA-inducible transactivation of ME1S1A, and provides new information on the Meis1 promoter.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 55-62).

No description available.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 97-114).

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 80-96).

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Virginia, 2007. / Spine title: Mechanism of tolerance to tyrosinase. Includes bibliographical references. Also available online through Digital Dissertations.

Ping Zhang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 131-144). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.